Slain Douglas, Miller Karla, Khakoo Rashida, Fisher Melanie, Wierman Trista, Jozefczyk Ken
School of Pharmacy, School of Medicine, West Virginia University, Morgantown 26506-9520, USA.
Clin Ther. 2002 Oct;24(10):1636-42. doi: 10.1016/s0149-2918(02)80066-2.
Lipid-based formulations of amphotericin B (AMB) have been shown to significantly lessen the occurrence of nephrotoxicity associated with the conventional form of AMB. A MEDLINE search of literature published from 1983 to 2002, using the search terms amphotericin B and nephrotoxicity, identified only 1 large, randomized, prospective trial that has tried to compare the nephrotoxicity rates among lipid-based AMB formulations. Using the nephrotoxicity surrogate marker of doubling of serum creatinine (SCr) level, the investigators reported a high rate of AMB lipid complex (ABLC)-associated nephrotoxicity (42.3%). However, enrollment in that study was limited to only febrile neutropenic patients.
This retrospective study estimated the rate of ABLC-associated nephrotoxicity in various clinical settings at a university hospital and compared that rate with previously reported rates of nephrotoxicity.
Data from adult neutropenic and nonneutropenic patients receiving ABLC were collected and the degree of nephrotoxicity was determined using 2 definitions: (1) doubling of baseline SCr level using the peak value within the first 7 days, and (2) end-of-therapy doubling of baseline SCr level using the end-of-therapy value.
Data from 33 patients (20 men, 13 women; mean age, 48.6 years) were collected. Using these definitions of ABLC-associated nephrotoxicity, only 2 cases (6.1%) were observed. This rate was significantly below the 42.3% rate reported in the only large published study (95% CI, 1.7-19.6; P < 0.001). The median change in SCr level was 0.1 mg/dL (range, -1.1 to 4.3 mg/dL). Rates of change were higher in patients who died during hospitalization, but the difference was not significant. Use of concomitant nephrotoxic agents did not account for significant changes in SCr level.
Data from this study suggest that ABLC infrequently causes clinically significant nephrotoxicity. Therefore, when formulary decisions are made in the selection of a drug for use in various clinical settings, earlier data derived from a single study in febrile neutropenic patients that suggested a significantly higher rate of nephrotoxicity should be interpreted cautiously. Larger trials with more diverse patient populations are needed to better characterize institutional rates of ABLC-associated nephrotoxicity and to aid formulary decision makers.
两性霉素B（AMB）的脂质体制剂已显示可显著降低与传统形式AMB相关的肾毒性发生率。使用搜索词“两性霉素B”和“肾毒性”对1983年至2002年发表的文献进行MEDLINE检索，仅发现1项大型随机前瞻性试验试图比较脂质体AMB制剂之间的肾毒性发生率。使用血清肌酐（SCr）水平翻倍这一肾毒性替代标志物，研究人员报告两性霉素B脂质复合物（ABLC）相关肾毒性发生率较高（42.3%）。然而，该研究的入组仅限于发热性中性粒细胞减少患者。
这项回顾性研究估计了某大学医院不同临床环境中ABLC相关肾毒性的发生率，并将该发生率与先前报道的肾毒性发生率进行比较。
收集接受ABLC治疗的成年中性粒细胞减少和非中性粒细胞减少患者的数据，并使用2种定义确定肾毒性程度：（1）使用前7天内的峰值使基线SCr水平翻倍，（2）使用治疗结束时的值使基线SCr水平在治疗结束时翻倍。
收集了33例患者（20例男性，13例女性；平均年龄48.6岁）的数据。使用这些ABLC相关肾毒性的定义，仅观察到2例（6.1%）。该发生率显著低于唯一一项已发表大型研究报告的42.3%（95%可信区间，1.7 - 19.6；P < 0.001）。SCr水平的中位数变化为0.1mg/dL（范围，-1.1至4.3mg/dL）。住院期间死亡患者的变化率较高，但差异不显著。同时使用肾毒性药物并未导致SCr水平出现显著变化。
本研究数据表明ABLC很少引起具有临床意义的肾毒性。因此，在为不同临床环境选择药物做出处方决策时，对于早期来自一项针对发热性中性粒细胞减少患者的研究中显示肾毒性发生率显著较高的数据应谨慎解读。需要开展更多不同患者群体的大型试验，以更好地描述机构内ABLC相关肾毒性的发生率，并帮助处方决策者。
